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In vitro study of drug-eluting stent coatings based on poly(l-lactide) incorporating cyclosporine A – drug release, polymer degradation and mechanical integrity

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Abstract

In this study, absorbable polymer stent coatings for localized drug delivery based on poly(l-lactide) (PLLA) and cyclosporine A (CsA) were developed and tested in vitro. Metallic stents were coated with different compositions of PLLA/CsA (70/30, 60/40, 50/50% w/w) and β-sterilized. The specimens were used to assess the drug release kinetics with HPLC. Sterilization influenced polymer degradation was measured with GPC. Mechanical integrity of the stent coatings was studied with SEM. The interconnection of the coated stents with a balloon-catheter was characterized by the measurement of stent dislodgment force. A migration assay was used to determine the inhibitory effect of the model drug CsA on smooth muscle cell (SMC) migration. The release of CsA was established over time periods up to 24 days in sodium chloride solution and in porcine blood plasma. An inhibition of SMC migration (max. 26–33%) was found for CsA concentrations of 4 × 10−5 to 4 × 10−7 mol/l. Marked molecular weight reduction (70–80%) of the PLLA matrix occurred after β-sterilization. We also observed a substantial decrease of in vitro degradation time. The maintenance of the mechanical integrity of the polymer coating during crimping and dilation of the specimens could be verified, and a sufficient stent dislodgment force of 0.8–0.9 N was measured.

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References

  1. P. J. De FEYTER, J. VOS and B. J. RENSING, Curr. Interv. Cardiol. Rev. 2 (2000) 326

    Google Scholar 

  2. G. S. MINTZ, J. J. POPMA, A. D. PICHARD, K. M. KENT, L. F. SATLER, S. C. WONG, M. K. HONG, J. A. KOVACH and M. B. LEON, Circulation 94 (1996) 35

    CAS  Google Scholar 

  3. R. HOFFMAN, G. S. MINTZ, G. R. DUSSAILLANT, J. J. PAOPMA, A. D. PICHARD, L. F. SATLER, K. M. KENT, J. GRIFFIN and M. B. LEON, Circulation 94 (1996) 1247

    Google Scholar 

  4. R. FATTORI and T. PIVA, Lancet North Am. Ed. 361 (2003) 247

    Google Scholar 

  5. J. E. SOUSA, P. W. SERRUYS and M. A. COSTA, Circulation 107 (2003) 2274 (Part I), 2283 (Part II)

  6. K. J. SALU, J. M. BOSMANS, H. BULT and C. J. VRINTS, Acta Cardiol. 59 (2004) 51

    Article  Google Scholar 

  7. R. S. SCHWARTZ, E. EDELMAN, A. CARTER, N. CHRONOS, C. ROGERS, K. A. ROBINSON, R. WAKSMAN, J. WEINBERGER, R. L. WILENSKY, D. N. JENSEN, B. D. ZUCKERMAN and R. VIRMANI, Circulation 106 (2002) 1867

    Article  Google Scholar 

  8. T. TSUJI, H. TAMAI, K. IGAKI, E. KYO, K. KOSUGA, T. HATA, M. OKADA, T. NAKAMURA, S. FUJITA, S. TAKEDA, S. MOTOHARA and H. UEHATA, Int. J. Cardiovasc. Intervent. 5 (2003) 13

    Article  Google Scholar 

  9. F. VOGT, A. STEIN, G. RETTEMEIER, N. KROTT, R. HOFFMANN, J. vom DAHL, A. K. BOSSERHOFF, W. MICHAELI, P. HANRATH, C. WEBER and R. BLINDT, Eur. Heart. J. 25 (2004) 1330

    Article  CAS  Google Scholar 

  10. K. J. SALU, J. M. BOSMANS, H. BULT and C. J. VRINTS, Acta Cardiol. 59 (2004) 165

    Article  Google Scholar 

  11. E. REGAR, G. SIANOS and P. W. SERRUYS, Brit. Med. Bull. 59 (2001) 227

    Article  CAS  Google Scholar 

  12. S. V. RANADE, K. M. MILLER, R. E. RICHARD, A. K. CHAN, M. J. ALLEN.and M. N. HELMUS, J. Biomed. Mater. Res. 71 (2004) 625

    Article  CAS  Google Scholar 

  13. P. J. MOHACSI, D. TÜLLER, B. HULLIGER and P. L. J. WIJNGAARD, J. Heart Lung Transplant. 16 (1997) 484

    CAS  Google Scholar 

  14. J. I. MOON, Y. S. KIM, M. S. KIM, E. H. KIM, H. J. KIM, S. I. KIM and K. Park, Transplant. Proc. 32 (2000) 2026

    Article  CAS  Google Scholar 

  15. B. M. MEISER, M. E. BILLINGHAM and R. E. MORRIS, Lancet 338 (1991) 1297

    Article  CAS  Google Scholar 

  16. R. L. STOLTENBERG, J. GERAGHTY, D. M. STEELE, E. KENNEDY, D. A. HULLETT and H. W. SOLLINGER, Transplantation 60 (1995) 993

    Article  CAS  Google Scholar 

  17. T. SAITO, A. IGUCHI, M. SAKURAI and K. TABAYASHI, Ann. Thorac. Surg. 77 (2004) 684

    Article  Google Scholar 

  18. T. W. TALBERT, J. R. GREEN, D. P. MUKHERJEE, A. L. OGDEN, R. H. MAYEUX, J. Long Term Eff. Med. Implants 13 (2003) 319

    Article  Google Scholar 

  19. A. P. TESTA PEZZIN, T. P. CARDOSO, M. do CARMO ALBERTO RINCON, C. A. de CARVALHO ZAVAGLIA, E. A. de REZENDE DUEK, Artif. Organs. 27 (2003) 428

    Article  Google Scholar 

  20. P. MAKELA, T. POHJONEN, P. TORMALA, T. WARIS and N. ASHAMMAKHI, Biomaterials 23 (2002) 2587

    Article  CAS  Google Scholar 

  21. A. K. CHEPUROV, G. G. KRIVOBORODOV, A. V. ZUBAREV , N. V. ZAITSEV and N. I. MARKINA, Urologiia 3 (2003) 44

    Google Scholar 

  22. T. ISOTALO, M. TALJA, T. VALIMAA, P. TORMALA and T. L. TAMMELA, J. Endourol. 16 (2002) 759

    Article  CAS  Google Scholar 

  23. M. MULTANEN, T. L. TAMMELA, M. LAURILA, J. SEPPALA, T. VALIMAA, P. TORMALA and M. TALJA, Urol. Res. 30 (2002) 227

    Article  CAS  Google Scholar 

  24. T. TSUJI, H. TAMAI, K. IGAKI, E. KYO, K. KOSUGA, M. OKADA, T. NAKAMURA, S. FUJITA, S. TAKEDA, S. MOTOHARA and H. UEHATA, Circulation 106 II (2002) 356

    Google Scholar 

  25. N. GRABOW, H. MARTIN and K.-P. SCHMITZ, Biomed. Tech. (Berlin) 47 Suppl 1 (2002) 503

    Article  Google Scholar 

  26. M. SCHLUN, K. STERNBERG, N. GRABOW, N. HAKANßON, S. KRAMER and K.-P. SCHMITZ, Biomed. Tech. (Berlin) 48 Suppl 1 (2003) 390

    Google Scholar 

  27. G. RAJASUBRAMANIAN, R. S. MEIDELL, C. LANDAU, M. L. DOLLAR, D. B. HOLT, J. E. WILLARD, M. D. PRAGER, R. C. EBERHART, ASAIO J. 40 (1994) M584

    Article  CAS  Google Scholar 

  28. C. M. AGRAWAL, K. F. HAAS, D. A. LEOPOLD and H. CLARK, Biomaterials 13 (1992) 176

    Article  CAS  Google Scholar 

  29. K. J. ZHU, J. X. ZHANG, C. WANG, H. YASUDA, A. ICHIMARU and K. YAMAMOTO, J. Microencapsul. 20 (2003) 731

    Article  CAS  Google Scholar 

  30. K. T. NGUYEN, S. H. SU, A. SHENG, D. WAWRO, N. D. SCHWADE, C. F. BROUSE, P. E. GREILICH, L. TANG and R. C. EBERHART, Biomaterials 24 (2003) 5191

    Article  CAS  Google Scholar 

  31. M. ZILBERMAN, R. C. EBERHART and N. D. SCHWADE, J. Biomater. Sci. Polym. Ed. 13 (2002) 1221

    Article  CAS  Google Scholar 

  32. M. LABINAZ, J. P. ZIDAR, R. S. STACK and H. R. PHILLIPS, J. Interv. Cardiol. 8 (1995) 395

    Article  CAS  Google Scholar 

  33. H. TAMAI, K. IGAKI, E. KYO, K. KOSUGA, A. KAWASHIMA, S. MATSUI, H. KOM, T. TSUJI, S. MOTOHARA and H. UEHATA, Circulation 102 (2000) 399

    CAS  Google Scholar 

  34. H. BARDELMEIJER, M. OUWEHAND, J. H. BEIJNEN, J. H. M. SCHELLENS and O. van TELLINGEN, J. Chromatogr. B. Biomed. Appl. 763 (2001) 201

    Article  CAS  Google Scholar 

  35. E. W. FISCHER, H. J. STERZEL and G. WEGNER, Kolloid-Z. u. Z. Polymere 251 (1973) 980

    Article  CAS  Google Scholar 

  36. B. KALB and A. J. PENNINGS, Polymer 21 (1980) 607

    Article  CAS  Google Scholar 

  37. D.H. LEWIS, in Biodegradable Polymers as Drug Delivery Systems, edited by M. Chasin and R. Langer (New York: Marcel Dekker, 1990) pp. 8, 24

  38. Arzneistoff-Profile, Basisinformation über arzneiliche Wirkstoffe, Govi-Verlag GmbH, Pharmazeutischer Verlag, Frankfurt am Main, ASP-7. Erg.-Lieferung (1990) 1–8

  39. P. NUGROHO, H. MITOMO, F. YOSHII and T. KUME, Polym. Degrad. Stab. 72 (2001) 337

    Article  CAS  Google Scholar 

  40. J. P. NUUTINEN, C. CLERC, T. VIRTA and P. TÖRMÄLÄ, J. Biomater. Sci. Polym. Edn. 13 (2002) 1325

    Article  CAS  Google Scholar 

  41. N. GRABOW, M. SCHLUN, K. STERNBERG, N. HAKANßON, S. KRAMER, and K.-P. SCHMITZ, J. Biomech. Eng. 127 (2005) 25

    Article  Google Scholar 

  42. P. MAINIL-VARLET, R. CURTIS and S. GOGOLEWSKI, J. Biomed. Mater. Res. 36 (1997) 360

    Article  CAS  Google Scholar 

  43. S. LI, H. GARREAU and M. VERT, J. Mater. Sci. Mater. Med. 1 (1990) 198

    Article  CAS  Google Scholar 

  44. R. SUURONEN, T. POHJONEN, J. HIETANEN and C. LINDQUIST, J. Oral. Maxillofac. Surg. 56 (1998) 604

    Article  CAS  Google Scholar 

  45. S. IANNACE, A. MAFFEZZOLI, G. LEO and L. NICOLAIS, Polymer 42 (2001) 3799

    Article  CAS  Google Scholar 

  46. M. ZILBERMAN, N. D. SCHWADE, R. S. MEIDELL and R. C. EBERHART, J Biomater. Sci. Polym. Ed. 12 (2001) 875

    Article  CAS  Google Scholar 

  47. S. GOGOLEWSKI, M. JOVANOVIC, S. M. PERREN, J. G. DILLON and M. K. HUGHES, J. Biomed. Mater. Res. 27 (1993) 1135

    Article  CAS  Google Scholar 

  48. A. M. LINCOFF, J. G. FURST, S. G. ELLIS, R. J. TUCH, E. J. TOPOL, J. Am. Coll. Cardiol. 29 (1997) 808

    Article  CAS  Google Scholar 

  49. H. PISTNER, Osteosynthese mit bioresorbierbaren Materialien, Einhorn-Presse Verlag, Reinbek (1999) 66–86

    Google Scholar 

  50. T. FREIER, C. KUNZE, C. NISCHAN, S. KRAMER, K. STERNBERG, M. SAß, U. T. HOPT, K. -P. SCHMITZ, Biomaterials 23 (2002) 2649

    Article  CAS  Google Scholar 

  51. S. J. HU R. FERNANDEZ, J. W. JONES Jr., Transplant. Proc. 31 (1999) 663

    Article  Google Scholar 

  52. M. S. KIM H. HA, Y. S. KIM, J. PARK, H. KIM, J. SEO, J. H. LEE and K. PARK, Transplant. Proc. 35 (2003) 189

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Andrea Rohde and Babette Hummel for expert technical assistance and Helga Rohde for assistance in the migration experiments. Roland Rohde (LEBAO Hannover) is gratefully acknowledged for his support in the microscopic and preparative work. The authors are furthermore grateful to Prof. Axel Haubold for helpful notes and suggestions. Biotronik GmbH & Co. KG, Berlin, Germany, is acknowledged for the generous supply of the metallic stent specimens. The work was financially supported by the German Federal Ministry of Education and Research within the program NBL3 (FKZ 01 ZZ 0108).

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  1. Institute for Biomedical Engineering, University of Rostock, Ernst-Heydemann-Str. 6, 18057, Rostock, Germany

    Katrin Sternberg, Sven Kramer, Claudia Nischan, Niels Grabow, Thomas Langer & Klaus-Peter Schmitz

  2. Institute for Experimental Pharmacology, University of Rostock, Schillingallee 70, 18057, Rostock, Germany

    Gerhard Hennighausen

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  1. Katrin Sternberg
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Correspondence to Katrin Sternberg.

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Sternberg, K., Kramer, S., Nischan, C. et al. In vitro study of drug-eluting stent coatings based on poly(l-lactide) incorporating cyclosporine A – drug release, polymer degradation and mechanical integrity. J Mater Sci: Mater Med 18, 1423–1432 (2007). https://doi.org/10.1007/s10856-007-0148-8

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